CN109238777B - Biochip micro quantitative sampling system - Google Patents
Biochip micro quantitative sampling system Download PDFInfo
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- CN109238777B CN109238777B CN201811139437.8A CN201811139437A CN109238777B CN 109238777 B CN109238777 B CN 109238777B CN 201811139437 A CN201811139437 A CN 201811139437A CN 109238777 B CN109238777 B CN 109238777B
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- 238000000018 DNA microarray Methods 0.000 title claims abstract description 34
- 238000005070 sampling Methods 0.000 title claims abstract description 28
- 239000007788 liquid Substances 0.000 claims abstract description 72
- 238000007664 blowing Methods 0.000 claims abstract description 58
- 238000001914 filtration Methods 0.000 claims description 89
- 210000004369 blood Anatomy 0.000 claims description 72
- 239000008280 blood Substances 0.000 claims description 72
- 239000012528 membrane Substances 0.000 claims description 48
- 238000002347 injection Methods 0.000 claims description 34
- 239000007924 injection Substances 0.000 claims description 34
- 210000003743 erythrocyte Anatomy 0.000 claims description 27
- 238000009825 accumulation Methods 0.000 claims description 21
- 238000007789 sealing Methods 0.000 claims description 12
- 238000009434 installation Methods 0.000 claims description 4
- 238000004891 communication Methods 0.000 claims description 2
- 210000002381 plasma Anatomy 0.000 description 22
- 238000000034 method Methods 0.000 description 9
- 238000001514 detection method Methods 0.000 description 7
- 238000012360 testing method Methods 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 5
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- 230000006835 compression Effects 0.000 description 4
- 238000007906 compression Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000000717 retained effect Effects 0.000 description 4
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 238000003672 processing method Methods 0.000 description 2
- 230000002411 adverse Effects 0.000 description 1
- 238000013473 artificial intelligence Methods 0.000 description 1
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- 238000011002 quantification Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/02—Devices for withdrawing samples
- G01N1/10—Devices for withdrawing samples in the liquid or fluent state
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- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
The invention discloses a biochip micro quantitative sampling system, which comprises a quantitative pipe, wherein a sample outlet is formed in the bottom of the quantitative pipe; the quantitative tube comprises a shell, a quantitative tube, a gas outlet, a quantitative tube lower section, a gas outlet and a gas passing channel, wherein the quantitative tube lower section is provided with a gas outlet; the sample outlet is positioned in the view field range of the camera unit, and the camera unit and the air blowing unit are electrically connected with the controller; the controller is used for calculating the liquid drop volume according to the liquid drop image and controlling the output quantity of the blowing unit according to the liquid drop volume. The invention uses a non-contact liquid drop mode to blow the quantitative sample liquid drop adhered and suspended at the sample outlet at the tail end of the quantitative tube into the biochip reactor, so that the sample is not polluted, and the quantitative accuracy of the sample is high; meanwhile, the structure is simple, the cost is low, and the constancy is good.
Description
Technical Field
The invention belongs to the technical field of biochip detection, and particularly relates to a microchip micro quantitative sampling system.
Background
When the conventional trace liquid sampling structure comprises a quantitative pipe, firstly, air in the quantitative pipe is discharged, trace liquid is quantitatively sucked from a certain container to the quantitative pipe by utilizing a negative pressure principle, then the quantitative pipe is shifted (moved or rotated) to a designated position, and then the liquid is pushed out of the quantitative pipe by utilizing the air, so that the purpose of sampling is achieved.
The biochip technology has been rapidly developed in recent 20 years, particularly, the microfluidic technology, new material technology and artificial intelligence technology, so that the biochip technology gradually goes to industrialization.
In a micro biochip, since liquid cannot be pumped from the bottom to the top, only a liquid sample can be quantitatively added from above the chip, i.e., after the sample is added to the quantitative tube, the sample is quantitatively pushed out of the quantitative tube from a sample outlet formed in the bottom of the quantitative tube, and finally the sample falls into a reactor below the quantitative tube.
In order to improve sampling efficiency, sample quantity meeting one or more tests can be added into the quantitative pipe at one time when the sample is added, and the sample can be quantitatively pushed out of the quantitative pipe according to the requirement in each test when the sample is tested. Because the required sample volume is trace (below 50 microliters) when the biochip detects each time, trace liquid is pushed out from the quantitative pipe, and trace sample liquid drops after quantitative can adhere and hang at the sample outlet, because trace quantitative sample liquid drops dead weight is very little, can not rely on dead weight to fall into the reactor automatically, if the mode of using the contact liquid drops makes remaining liquid drops fall into the reactor, because liquid adhesion can not avoid adhering on contact sampling auxiliary structure, therefore use contact sampling auxiliary structure can not only pollute the sample, still can influence the quantitative precision of sample.
Furthermore, existing micro-fluid sampling structures require displacement during sampling and are therefore difficult or impossible to integrate into a tiny biochip. Meanwhile, the air is easily sucked into the metering tube in the mode, so that the situation that the air is mixed in the liquid and pushed out, and the air is brought into the reactor of the biochip to influence the detection result of the biochip on a sample is avoided.
In addition, in prior art, the blood structure is strained to the blood structure that all adopts the perpendicular form of straining to the plasma sample preparation that biochip detected usefulness, strains blood structure and includes the shell, is equipped with the filtration membrane that the level was placed in the shell, and the shell top is equipped with the first cavity that the opening was up, is equipped with the second cavity that is located under the first cavity in the shell, communicates through filtration membrane between first cavity and the second cavity. When filtering blood, firstly, whole blood is added into the first cavity, then the first cavity is pressurized in a sealing way, the blood plasma with small molecules passes through the filtering membrane below the first cavity to enter the second cavity, and the red blood cells with large molecules are retained in the first cavity, so that the purpose of filtering blood is achieved.
In the above-mentioned vertical blood filtering structure, because the red blood cells stagnate in the first cavity and can deposit on the filtration membrane of the bottom of first cavity, along with the progression of straining blood, the concentration of red blood cells in the first cavity is higher and higher to it leads to the fact straining blood inadequately to block up the filtration membrane easily, and the time that the sample of filtration unit volume needs is prolonged, and efficiency reduces, probably presses broken red blood cells even, causes the sample inefficacy.
Disclosure of Invention
In the prior art, a manner of contacting the liquid drops is used to enable quantitative micro sample liquid drops adhered and suspended at a sample outlet at the tail end of a quantitative tube to fall into a biochip reactor, so that a sample can be polluted, and the quantitative precision of the sample can be influenced. The invention aims to overcome the defects of the prior art, and provides a biochip micro quantitative sampling system, which uses a non-contact liquid drop mode to blow quantitative micro sample liquid drops adhered and suspended at a sample outlet at the tail end of a quantitative pipe into a biochip reactor, so that a sample is not polluted, and the quantitative precision of the sample is high; meanwhile, the structure is simple, the cost is low, and the constancy is good; in addition, the negative pressure suction sample is not required to be formed by exhausting air, so that the negative pressure suction sample is easy to be directly integrated in a tiny biological chip; when in sample injection, a section of liquid column without air can be formed in the quantitative tube, so that air is prevented from being mixed in a reactor of a biochip to be brought into a sample, and the detection result of the sample is not affected; meanwhile, red blood cells are not easy to block a filtering membrane during preparation of the plasma sample, blood filtering is complete, blood filtering time is short, efficiency is high, and the compression risk of the red blood cells is low.
In order to solve the technical problems, the invention adopts the following technical scheme:
a biochip micro quantitative sampling system comprises a quantitative tube, wherein the bottom of the quantitative tube is provided with a sample outlet; the quantitative tube is characterized by also comprising a shell, an air blowing unit, a camera unit and a controller, wherein the shell is provided with a mounting through hole, the lower section of the quantitative tube stretches into the mounting through hole, the side wall of the shell is provided with an air blowing through hole which is communicated with the air outlet of the air blowing unit and the lower section of the quantitative tube, and an air passing channel which is communicated with the air blowing through hole and the outer wall of the sample outlet is formed between the lower section of the quantitative tube and the mounting through hole; the sample outlet is positioned in the view field range of the camera unit, and the camera unit and the air blowing unit are electrically connected with the controller; the camera unit is used for collecting the liquid drop image at the sample outlet, and the controller is used for calculating the liquid drop volume according to the liquid drop image and controlling the output quantity of the blowing unit according to the liquid drop volume, so that quantitative sample liquid drops with different sizes at the sample outlet can be blown down vertically.
After each quantitative push-out of the sample liquid by the quantitative tube, a quantitative trace of sample droplet is adhered and hung at the sample outlet. At this time, the air blowing unit is utilized to blow air to the direction of the sample outlet through the air blowing through hole and the air passing channel in sequence, so that quantitative micro sample drops adhered to the sample outlet can be blown off, the sample is not polluted, and the quantitative precision of the sample is ensured.
The image pick-up unit can shoot a liquid drop image at the sample outlet, meanwhile, the image pick-up unit sends collected data to the controller, the controller calculates the volume of the liquid drop according to an image processing method, and the controller controls the output quantity of the air blowing unit according to the volume of the liquid drop. The liquid drop volume is large, the air blowing amount of the air blowing unit is large, the air pressure is large, and the time is long; the liquid drop volume is small, the air blowing amount of the air blowing unit is small, the air pressure is small, and the time is short. The controller is utilized to automatically control blowing according to the volume of the liquid drops, so that the accurate vertical blowing of the liquid drops of samples with different sizes can be ensured.
The micro-scale quantification of the present invention means that the sample amount of the sample pushed out from the sample outlet of the quantifying tube is 3 ul to 100ul at a time.
As a preferable mode, the installation through hole is a conical hole with a large upper part and a small lower part.
The air passing channel formed by the structure can change the flowing direction of air, effectively collect air flow, ensure that the air is concentrated to blow to the upper part of liquid drops adhered to the sample outlet, ensure that the liquid drops can vertically fall into a designated area below the sample outlet and cannot be blown off, and further ensure the quantitative precision of the sample.
As a preferable mode, the middle section of the outer side wall of the quantitative tube is attached to the shell.
As a preferable mode, the middle section of the quantitative pipe is also provided with a step part for preventing the upward flow of air.
The quantitative pipe with the structure can prevent air from flowing upwards on one hand, and can ensure the positioning of the quantitative pipe in the shell on the other hand.
As a preferred mode, the air blowing unit comprises an air pump and an air pipe connected with an air outlet of the air pump, wherein the control end of the air pump is electrically connected with the output end of the controller, and the air outlet of the air pipe is opposite to the air blowing through hole.
Further, the quantitative blood filtering device also comprises a blood filtering structure, wherein the top of the quantitative tube is provided with a quantitative plunger for sealing and sealing the inner cavity of the quantitative tube, and the upper part of the side wall of the quantitative tube is provided with a sample injection port communicated with the inner cavity of the quantitative tube; the plasma outlet of the hemofilter structure is communicated with the sample injection port.
By means of the structure, after the whole blood is filtered by the blood filtering structure to obtain the plasma sample, the plasma sample is injected into the inner cavity of the quantitative tube from the plasma outlet of the blood filtering structure through the sample injection opening, the sample automatically enters the inner cavity of the quantitative tube due to the sealing of the upper end and the opening of the lower end of the quantitative tube, air in the quantitative tube is continuously pushed out from the sample outlet by the sample in the sample injection process, the sample amount injected into the inner cavity of the quantitative tube is controlled, and finally, a section of sample liquid column without air is formed in the quantitative tube, so that the accurate quantitative sampling is possible. Finally, the quantitative plunger is pressed downwards, so that the sample in the quantitative tube can be pushed out as required. The invention can be directly integrated in a micro biochip because the negative pressure suction sample is not required to be formed by exhausting air; since the liquid column without air can be formed in the quantitative tube, the sample with air is prevented from being added into the reactor of the biochip, and the detection result of the sample is not adversely affected.
As a preferred mode, in the initial sample injection state, the bottom surface of the quantitative plunger is coplanar with the highest point of the sample injection port; or the bottom surface of the dosing plug is positioned between the highest point and the lowest point of the sample injection port.
The formation of an air-free sample fluid column is further facilitated when the bottom surface of the metering plunger is located between the highest point and the lowest point of the sample injection port.
As a preferred mode, the height of the sample injection opening is 1 mm-2.5 mm, and the pipe diameters of the middle section and the upper section of the quantitative pipe are 0.5 mm-3.5 mm. The tube diameter of the quantitative tube is designed according to the viscosity of the fluid (blood plasma), so that the air in the sample injection process can be conveniently discharged.
Further, the blood filtering structure comprises a filtering membrane arranged in the shell, a first cavity and a second cavity, wherein the opening of the first cavity is upward, the second cavity is communicated with the first cavity through the filtering membrane, and the filtering membrane is vertical to the horizontal plane; the second cavity is in communication with the sample injection port.
By means of the structure, the filtering membrane is vertical to the horizontal plane, and is horizontally arranged relative to the filtering membrane in the prior art, and the filtering membrane is vertically arranged on the side edge of the first cavity. Even if erythrocytes are retained in the first cavity in the blood filtering process, due to the vertical arrangement of the filtering membrane, erythrocytes are deposited at the bottom of the first cavity, so that erythrocytes are not easy to block the filtering membrane arranged at the side edge of the first cavity, blood plasma is smooth through the filtering membrane, blood filtering is complete, blood filtering time is short, efficiency is high, and meanwhile, the compression risk of erythrocytes is low.
Further, a pressure cavity is further arranged in the shell and is communicated with the bottom of the first cavity, the volume of the pressure cavity is smaller than that of the first cavity, the pressure cavity is communicated with the second cavity through a filtering membrane, and the volume of the pressure cavity is larger than or equal to the total volume of red blood cells in whole blood to be filtered.
By means of the structure, the bottom of the first cavity is communicated with the pressure accumulation cavity, whole blood to be filtered in the first cavity is continuously conveyed into the pressure accumulation cavity, then plasma passes through the filtering membrane to enter the second cavity, and erythrocytes are retained in the pressure accumulation cavity, so that the purpose of filtering blood is achieved. Because the volume of the packed cavity is larger than or equal to the total volume of red blood cells in whole blood to be filtered, the red blood cells are deposited at the bottom of the packed cavity in the blood filtering process, and the space above the packed cavity is reserved for receiving newly injected whole blood, so that the filtering membrane is less prone to being blocked by the red blood cells, and the blood filtering is smoother.
Further, the blood filtering plunger can be sealed and sealed on the top opening of the first cavity.
When filtering blood, the driving mechanism is used for applying driving force to the blood filtering plunger, so that the blood filtering plunger can be used for sealing and pressurizing the first cavity, and whole blood can be promoted to flow towards the filtering membrane, and the purpose of filtering blood can be achieved. When the blood filtering plunger is in operation, the blood filtering plunger cannot press the blood pressing cavity, and because redundant sample plasma is filtered from the filtering membrane to the second cavity, the whole blood volume is reduced, so that the blood pressing cavity is in a non-pressure state, and the risk of pressing red blood cells does not exist.
As a preferable mode, the highest point of the side surface of the pressure accumulation cavity connected with the filtering membrane and the highest point of the opposite side surface are on the same horizontal plane; alternatively, the highest point of the side surface of the pressure accumulation cavity connected with the filtering membrane is higher than the highest point of the opposite side surface.
Under the condition that the highest point of the connecting side surface of the pressure accumulation cavity and the filtering membrane is higher than the highest point of the opposite side surface, the filtering membrane is less prone to being blocked.
Compared with the prior art, the quantitative micro sample liquid drop adhered and suspended at the sample outlet at the tail end of the quantitative tube is blown into the biochip reactor in a non-contact liquid drop mode, so that the sample cannot be polluted, and the quantitative accuracy of the sample is high; meanwhile, the structure is simple, the cost is low, and the constancy is good; the negative pressure suction sample is not required to be formed by exhausting air, so that the negative pressure suction sample is easy to be directly integrated in a micro biochip; when in sample injection, a section of liquid column without air can be formed in the quantitative tube, so that air is prevented from being mixed in a reactor of a biochip to be brought into a sample, and the detection result of the sample is not affected; meanwhile, red blood cells are not easy to block a filtering membrane during preparation of a plasma sample, blood filtering is complete, blood filtering time is short, efficiency is high, compression risk of red blood cells is low, the sample is not easy to pollute, the method is particularly suitable for preparation of a biochip plasma test sample, test cost is greatly reduced, and test efficiency is improved.
Drawings
FIG. 1 is a schematic diagram of an embodiment of a microchip micro quantitative sampling system.
Wherein 1 is a housing, 101 is a first cavity, 102 is a second cavity, 103 is a pressure accumulation cavity, 105 is a mounting through hole, 106 is an air blowing through hole, 2 is a filtering membrane, 3 is a blood filtering plunger, 4 is a quantifying tube, 401 is a sample injection port, 402 is a sample outlet, 403 is a step part, 5 is a quantifying plunger, 6 is an air blowing unit, 7 is an air passing channel, 8 is an image pickup unit, 9 is a controller, 10 is a reactor, and 11 is a sample adding channel.
Detailed Description
As shown in fig. 1, the biochip micro quantitative sampling system comprises a quantitative tube 4, wherein a sample outlet 402 is formed in the bottom of the quantitative tube 4; the quantitative tube quantitative detection device also comprises a shell 1, an air blowing unit 6, a camera unit 8 and a controller 9, wherein a mounting through hole 105 is formed in the shell 1, the lower section of the quantitative tube 4 stretches into the mounting through hole 105, an air blowing through hole 106 which is used for communicating the air outlet of the air blowing unit 6 with the lower section of the quantitative tube 4 is formed in the side wall of the shell 1, and an air passing channel 7 which is used for communicating the air blowing through hole 106 with the outer wall of the sample outlet 402 is formed between the lower section of the quantitative tube 4 and the mounting through hole 105; the sample outlet 402 is positioned in the field of view of the camera unit 8, and the camera unit 8 and the blowing unit 6 are electrically connected with the controller 9; the camera unit 8 is used for acquiring a liquid drop image at the sample outlet 402, and the controller 9 is used for calculating the liquid drop volume according to the liquid drop image and controlling the output quantity of the air blowing unit 6 according to the liquid drop volume so that quantitative sample liquid drops with different sizes at the sample outlet 402 can be blown off vertically.
In fig. 1, the air outlet of the air blowing unit 6 is disposed on the side of the air blowing through hole 106, in practice, the air outlet of the air blowing unit 6 may be set according to the actual situation, that is, the distance between the air outlet of the air blowing unit 6 and the housing 1 may be adjusted according to the actual situation, and whether the air outlet of the air blowing unit 6 needs to extend into the housing 1 may be set according to the actual situation. Meanwhile, the air blowing direction of the air outlet of the air blowing unit 6 can be set according to the requirement, and the air blowing direction can be all directions of the upper, lower, left and right directions of the air blowing through hole, can be used for transversely blowing air, can be used for vertically blowing air, and can be used for obliquely blowing air.
After each quantitative push-out of the sample liquid by the metering tube 4, a quantitative trace of sample droplet adhesion hangs at the sample outlet 402. At this time, the air blowing unit 6 is used to blow air to the direction of the sample outlet 402 through the air blowing through hole 106 and the air passing channel 7 in sequence, so that the quantitative sample liquid drops adhered to the sample outlet 402 can be blown off, the sample is not polluted, and the quantitative accuracy of the sample is ensured.
The image pick-up unit 8 can shoot the liquid drop image at the sample outlet 402, meanwhile, the image pick-up unit 8 sends collected data to the controller 9, the controller 9 calculates the volume of liquid drops according to an image processing method, the controller 9 controls the output quantity of the air blowing unit 6 according to the volume of the liquid drops, and therefore the fact that sample liquid drops with different sizes can be accurately blown down vertically can be guaranteed. The liquid drop volume is large, the air blowing amount of the air blowing unit 6 is large, the air pressure is large, and the time is long; the liquid drop volume is small, and then the blowing unit 6 has small blowing amount, small air pressure and short time.
After the drop is blown off, a small portion remains at the end of the metering tube 4 (air cannot completely blow all the liquid), but this portion remains stable every time, and is contained when the metering tube 4 discharges the sample quantitatively, so that the accuracy of the metering is not affected.
The mounting through hole 105 is a conical hole with a large upper part and a small lower part.
The air passing channel formed by the structure can change the flowing direction of air, effectively collect air flow, ensure that the air is concentrated to blow to the upper part of liquid drops adhered to the sample outlet, ensure that the liquid drops can vertically fall into a designated area below the sample outlet and cannot be blown off, and further ensure the quantitative precision of the sample.
The middle section of the outer side wall of the metering tube 4 is attached to the shell 1.
The middle section of the metering tube 4 is also provided with a step 403 for preventing air from flowing upward.
The quantitative pipe with the structure can prevent air from flowing upwards on one hand, and can ensure the positioning of the quantitative pipe in the shell on the other hand.
The biochip micro quantitative sampling system further comprises an image pick-up unit 8 and a controller 9, the sample outlet 402 is located in the field of view of the image pick-up unit 8, and the image pick-up unit 8 and the air blowing unit 6 are electrically connected with the controller 9.
The air blowing unit 6 comprises an air pump and an air pipe connected with an air outlet of the air pump, a control end of the air pump is electrically connected with an output end of the controller 9, and the air outlet of the air pipe is opposite to the air blowing through hole 106.
The invention also comprises a blood filtering structure, wherein the top of the quantifying tube 4 is provided with a quantifying plunger 5 for sealing and sealing the inner cavity of the quantifying tube 4, and the upper part of the side wall of the quantifying tube 4 is provided with a sample injection port 401 communicated with the inner cavity of the quantifying tube 4; the plasma outlet of the hemofilter structure communicates with the sample injection port 401. The dosing plunger 5 may be of different materials and thicknesses as desired.
After the whole blood is filtered by the blood filtering structure to obtain a plasma sample, the plasma sample is injected into the inner cavity of the quantitative tube 4 from the plasma outlet of the blood filtering structure through the sample injection opening 401, and the sample automatically enters the inner cavity of the quantitative tube 4 due to the sealing of the upper end and the opening of the lower end of the quantitative tube 4, in the sample injection process, the air in the quantitative tube 4 is continuously pushed out from the sample outlet 402 by the sample, the sample amount injected into the inner cavity of the quantitative tube 4 is controlled, and finally, a section of sample liquid column without air is formed in the quantitative tube 4, so that the possibility of accurate quantitative sampling is provided. Finally, the sample in the dosing tube 4 can be pushed out as required by pressing down the dosing plunger 5. The invention can be directly integrated in a micro biochip because the negative pressure suction sample is not required to be formed by exhausting air; because the liquid column without air can be formed in the quantitative tube 4, the phenomenon that the air mixed with the sample enters the reactor of the biochip during sample injection is avoided, and the detection result of the sample is not affected.
In the initial sample injection state, the bottom surface of the quantitative plunger 5 is coplanar with the highest point of the sample injection port 401; or the bottom surface of the metering plunger 5 is located between the highest point and the lowest point of the sample injection port 401. The formation of an air-free sample fluid column is further facilitated when the bottom surface of the metering plunger 5 is located between the highest point and the lowest point of the sample injection port 401.
The sample inlet 401 has an opening height of 1mm to 2.5mm, and the tube diameters of the middle and upper sections of the quantitative tube 4 are 0.5mm to 3.5mm. The tube diameter of the quantitative tube is designed according to the viscosity of the fluid (blood plasma), so that the air in the sample injection process can be conveniently discharged. The quantitative tube 5 may have other structures than the structure described in the embodiment, such as a rectangular parallelepiped structure.
The quantitative tube 4 is made of hydrophobic material, or the inner wall of the quantitative tube 4 is provided with a hydrophobic coating.
The inner surface of the quantitative tube 4 is a smooth surface.
The blood filtering structure comprises a filtering membrane 2 arranged in a shell 1, a first cavity 101 with an upward opening and a second cavity 102, wherein the first cavity 101 is communicated with the second cavity 102 through the filtering membrane 2, and the filtering membrane 2 is vertical to the horizontal plane; the second cavity 102 communicates with the sample injection port 401.
The shell 1 is also internally provided with a pressure cavity 103, the pressure cavity 103 is communicated with the bottom of the first cavity 101, the volume of the pressure cavity 103 is smaller than that of the first cavity 101, the pressure cavity 103 is communicated with the second cavity 102 through the filtering membrane 2, and the volume of the pressure cavity 103 is larger than or equal to the total volume of red blood cells in whole blood to be filtered.
By requiring the filtration to obtain the amount of plasma, the volume of whole blood to be filtered can be calculated, thereby obtaining the total volume of red blood cells in the whole blood. For example: if 20 microliters of plasma is required, since about 40-50% of the total blood is required, at least 50 microliters of total blood is required, and 25-30 microliters of red blood cells are present in 50 microliters of total blood, so that the volume of the hold-down chamber 103 is 25-30 microliters or slightly greater.
The pressure accumulation cavity 103 may be regular or irregular, such as square or rectangular.
Because the filtering membrane 2 is vertical to the horizontal plane, compared with the filtering membrane 2 in the prior art, the filtering membrane 2 in the invention is arranged on the side of the pressure accumulation cavity 103 vertically. The bottom of the first cavity 101 is communicated with the pressure accumulation cavity 103, whole blood to be filtered in the first cavity 101 is continuously conveyed into the pressure accumulation cavity 103, then plasma passes through the filter membrane 2 to enter the second cavity 102, and erythrocytes are retained in the pressure accumulation cavity 103, so that the purpose of filtering blood is achieved.
Because the volume of the pressure accumulation cavity 103 is greater than or equal to the total volume of red blood cells in whole blood to be filtered, the red blood cells are deposited at the bottom of the pressure accumulation cavity 103 in the blood filtering process, and the whole blood which is used for receiving new injection is reserved in the upper space of the pressure accumulation cavity 103, because the filtering membrane 2 is vertically arranged at the side edge of the pressure accumulation cavity 103, the filtering membrane 2 is not easy to be blocked by the red blood cells, the blood filtering is smoother, the blood filtering is complete, the blood filtering time is short, the efficiency is high, and meanwhile, the compression risk of the red blood cells is low.
The blood filtering structure also comprises a blood filtering plunger 3 which can be sealed and sealed with the top opening of the first cavity 101.
When filtering blood, firstly, whole blood is injected into the first cavity 101 from the sample adding channel 11, and then the driving mechanism is used for applying driving force to the blood filtering plunger 3, so that the blood filtering plunger 3 is used for sealing and pressurizing the first cavity 101, and the whole blood is promoted to flow towards the direction of the filtering membrane 2, thereby achieving the purpose of filtering blood. In operation, the plunger 3 is not pressed into the chamber 103, and the chamber 103 is in a non-pressure state, so that there is no risk of pressing red blood cells because the redundant sample plasma is filtered from the filter membrane 2 to the second chamber 102 and the volume of whole blood is reduced.
The height of the highest point of the side surface of the pressure chamber 103 connected with the filter membrane 2 relative to the horizontal plane is a, and the height of the highest point of the side surface of the pressure chamber 103 opposite to the filter membrane 2 relative to the horizontal plane is b, in this embodiment, a=b.
a may also be greater than b, which is not shown in the drawings, but does not affect the understanding and implementation of the present invention by those skilled in the art. When a > b, the filter membrane 2 is less prone to clogging.
The shell 1 is provided with an inserting port for inserting the filtering membrane 2. The insertion opening is arranged on the side wall of the shell 1, and the insertion opening can also be arranged at the top or the bottom of the shell 1. The periphery of the filtering membrane 2 is treated by soft rubber, and when the filtering membrane is installed, the filtering membrane 2 is in interference fit with the side wall of the insertion port, so that the sealing effect is achieved, and the side leakage of a sample is prevented from overflowing.
When the present invention is applied to a biochip, the biochip comprises a reactor 10 with an opening facing upwards, and the microchip micro quantitative sampling system, and the sample outlet 402 is located above the reactor 10.
The working process of the invention is as follows:
when the sample injection in the metering tube 4 is completed, firstly, the sample required by the single test is quantitatively discharged from the metering tube 4, a trace amount (less than 50 microliters) of sample liquid drops are formed at the sample outlet 402 of the metering tube 4 in an adhering mode, and the liquid drops are hung at the sample outlet 402. The air is blown out from the air outlet of the air pump, and after passing through the air blowing through hole 106, the blown air can only flow downward due to the blocking of the stepped portion 403. After the air flowing downwards is collected by the air passage 7, the air is intensively blown to the upper part of the liquid drop, so that the liquid drop vertically falls into the reactor 10, and the liquid drop cannot be blown off and splashed out of the reactor 10 or blown to the side wall of the reactor 10, thereby ensuring the quantitative precision of the sample.
Wherein the output of the air pump is controlled by the volume of the liquid drops calculated by the controller 9 according to the liquid drop images acquired by the image pick-up unit 8.
The embodiments of the present invention have been described above with reference to the accompanying drawings, but the present invention is not limited to the above-described embodiments, which are merely illustrative and not restrictive, and many forms may be made by those having ordinary skill in the art without departing from the spirit of the present invention and the scope of the claims, which are all within the scope of the present invention.
Claims (10)
1. A biochip micro quantitative sampling system comprises a quantitative tube (4), wherein a sample outlet (402) is formed in the bottom of the quantitative tube (4); the quantitative tube (4) is characterized by further comprising a shell (1), an air blowing unit (6), a camera shooting unit (8) and a controller (9), wherein an installation through hole (105) is formed in the shell (1), the lower section of the quantitative tube (4) stretches into the installation through hole (105), an air blowing through hole (106) for communicating an air outlet of the air blowing unit (6) with the lower section of the quantitative tube (4) is formed in the side wall of the shell (1), and an air passing channel (7) for communicating the air blowing through hole (106) with the outer wall of the sample outlet (402) is formed between the lower section of the quantitative tube (4) and the installation through hole (105); the sample outlet (402) is positioned in the field of view of the camera unit (8), and the camera unit (8) and the air blowing unit (6) are electrically connected with the controller (9); the camera unit (8) is used for collecting a liquid drop image at the sample outlet (402), and the controller (9) is used for calculating the liquid drop volume according to the liquid drop image and controlling the output quantity of the blowing unit (6) according to the liquid drop volume size, so that quantitative sample liquid drops with different sizes at the sample outlet (402) can be blown off vertically.
2. The microchip micro quantitative sampling system as claimed in claim 1, wherein the mounting through hole (105) is a conical hole with a large upper part and a small lower part.
3. The system for quantitative sampling of a microchip according to claim 1, wherein the middle section of the outer side wall of the quantitative tube (4) is attached to the housing (1).
4. The microchip micro quantitative sampling system as set forth in claim 1, wherein the middle section of the quantitative tube (4) is further provided with a step (403) for preventing the upward flow of air.
5. The microchip micro quantitative sampling system as defined in any one of claims 1 to 4, wherein the air blowing unit (6) comprises an air pump, an air pipe connected to the air outlet of the air pump, the control end of the air pump is electrically connected to the output end of the controller (9), and the air outlet of the air pipe is opposite to the air blowing through hole (106).
6. The biochip micro quantitative sampling system according to claim 1, further comprising a blood filtering structure, wherein a quantitative plunger sealing and sealing the inner cavity of the quantitative tube (4) is arranged at the top of the quantitative tube (4), and a sample injection port communicated with the inner cavity of the quantitative tube (4) is arranged at the upper part of the side wall of the quantitative tube (4); the plasma outlet of the hemofilter structure is communicated with the sample injection port.
7. The microchip micro quantitative sampling system as defined by claim 6, wherein in the initial sample injection state, the bottom surface of the quantitative plunger is coplanar with the highest point of the sample injection port; or the bottom surface of the dosing plug is positioned between the highest point and the lowest point of the sample injection port.
8. The system of claim 6, wherein the sample injection port has a height of 1mm to 2.5mm, and the middle and upper sections of the quantitative tube (4) have a diameter of 0.5mm to 3.5mm.
9. The biochip micro quantitative sampling system according to any one of claims 6 to 8, wherein the blood filtering structure comprises a filtering membrane arranged in the housing (1), a first cavity with an upward opening and a second cavity, wherein the first cavity is communicated with the second cavity through the filtering membrane, and the filtering membrane is vertical to the horizontal plane; the second cavity is in communication with the sample injection port.
10. The micro quantitative sampling system of biochip according to claim 9, wherein the housing (1) is further provided with a pressure accumulation cavity, the pressure accumulation cavity is communicated with the bottom of the first cavity, the volume of the pressure accumulation cavity is smaller than the volume of the first cavity, the pressure accumulation cavity is communicated with the second cavity through a filtering membrane, and the volume of the pressure accumulation cavity is larger than or equal to the total volume of red blood cells in whole blood to be filtered.
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| CN201811139437.8A CN109238777B (en) | 2018-09-28 | 2018-09-28 | Biochip micro quantitative sampling system |
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| CN201811139437.8A CN109238777B (en) | 2018-09-28 | 2018-09-28 | Biochip micro quantitative sampling system |
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| CN111707507B (en) * | 2020-06-23 | 2023-02-28 | 合肥安为康医学检验有限公司 | Biochemical quantitative detection device of blood sample |
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